Cancer is considered to be the leading cause of death in developed countries necessitating the development of novel anti-cancer agents. Worldwide colon cancer is one of the most prevalent types of cancer being the fourth most common cancer in men and the third in women. Conventionally, colon cancer can be treated by surgical ablation, however many colon cancers are discovered at an advanced stage when surgery alone is unable to cure the disease. As over 40% of colon cancer patients develop metastases chemotherapy and/or radiotherapy are used as an adjunctive to surgical means in order to treat the disease. However, these techniques are not always effective against highly metastasized stages of the disease and consequently the development of novel therapeutic means effective against advanced stages of colon cancer are essential.
A number of factors influence the risk of developing colon cancer, such as age and diet, although it is predominantly a genetic disease, resulting from DNA mutations. It is caused by the overexpression of oncogenes and the inactivation of tumour suppressor genes.
Currently, a major research initiative is being directed towards the identification and understanding of the biochemical mechanisms by which cell death is initiated. Cells die as a result of necrosis which occurs as a result of injury or by programmed cell death through apoptosis. When DNA is damaged in normal cells, it is either repaired or the cell undergoes apoptosis. In cancerous cells, DNA repair does not often occur and the apoptotic levels are extremely low. Several chemotherapeutic agents have been proven to induce apoptosis through underlying cellular mechanisms. The identification of apoptosis inducers presents a strong basis for the development of potential anti-cancer agents and furthermore, by apoptosis induction the novel compounds may reduce the resistance of colon cancer cells to current therapeutic regimes.
The search for novel drugs to be used in the treatment of colon cancer is essential in combating this life-threatening disease. Large-scale screening of compounds with potential anticancer activity is used to assess a broad range of pharmaceutical compounds, including both naturally occurring and synthesized chemical compounds. The primary aim of in vitro screening programmes is to identify biologically active compounds showing selective activity against certain tumour cell lines. These compounds can then be developed into novel chemotherapeutic drugs for the treatment of different types of cancer.
The use of multi-component chemical reactions in the synthesis of biologically active compounds displaying anti-cancer properties has been an area of prolific research in recent times. One of the classes of compounds that are accessible by multi-component chemical reactions are the imidazo[1,2-a]pyridines.